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Elaine Quilici is Pharmaceutical Executive's Senior Editor. Email her at email@example.com
Michael Henderson, Chief Business Officer, BridgeBio spoke to Pharm Exec about his efforts in developing potential treatments for rare diseases.
Sometimes you don’t have to start at square one when searching for solutions. When it comes to developing new therapies, researchers might be able to gain some knowledge from the shelves of academia or big pharma.
BridgeBio’s chief business officer, Michael Henderson, says sifting through this existing research could hold new hope. This is what he has done with infigratinib, repurposing a drug in development for oncology to potentially treat achondroplasia, the most common genetic cause of dwarfism, at much lower doses. Here, Henderson discusses his efforts and successes to date, and offers insights to others who might benefit from following this model.
Pharm Exec: How are you using genetics to inform drug development for rare disease?
Michael Henderson: We know the shelves of academia are lined with research breakthroughs that could become potential targeted therapeutics for genetic diseases. At BridgeBio, our mission is to uncover academia’s strong, early stage innovation around genetically driven conditions and move it into the clinic for further development, in the hopes of ultimately reaching patients as quickly and safely as possible.
For context, there are more than 7,000 identified rare genetic diseases, yet only a few hundred have approved treatments today. The Human Genome Project and advances in sequencing tools have empowered us to identify the genetic causes of these conditions, unveiling findings we can then use to work backward and potentially solve.
Since I joined the BridgeBio team roughly five years ago, we’ve taken on around 30 different programs, submitted more than 10 INDs and are on track to have filed two NDAs by the end of this year. To accomplish this, we’ve established a proactive strategy with multiple research and academic institutions to foster mutually beneficial, long-term partnerships rather than the traditional, one-off transactional approach. Once we acquire a compound, we build a small, but highly skilled and dedicated team to push it across the finish line.
One example of this is infigratinib, an FGFR inhibitor. A number of cancers can be driven by a fusion or mutation of the FGFR 1, 2, or 3 genes. Infigratinib targets the FGFR protein and blocks activity downstream in the pathway, which has been shown in clinical research studies to inhibit growth, as well as slow and in some case even regress the tumor. In our Phase 2 trial in cholangiocarcinoma, 84% of patients who received infigratinib had disease control (their tumors didn’t grow) and 27% had a clinical response, meaning their tumor got smaller. We acquired this drug from Novartis’ oncology shelf, not only because of its strong promise in cancer based on published data, but largely due to an academic paper that revealed a potential application (at a substantially lower dose) for achondroplasia, the most common genetic cause of dwarfism. By the end of the year we will have submitted our NDA for cholangiocarcinoma (bile duct cancer) and our clinical studies are underway in urothelial carcinoma (bladder cancer) and achondroplasia.
PE: What was your discovery around the drug infigratinib, and how did you go about acquiring it from Novartis in 2018?
Henderson: It began when we discovered a paper from Laurence Legeai-Mallet, PhD, head of the research team at Imagine Institute in Université de Paris. She and her institute discovered the genetic cause of dwarfism in 1994 and have led research in this field ever since. This particular paper showed the potential of infigratinib—a then-shelved cancer drug—to target the mutation at its source, with the potential to lead to increased bone growth.
Within a week of discovering the paper, we were in contact with Dr. Legeai-Mallet’s team. Not even a week after that, we were participating in an 11th-hour competitive bid. And in under four months, we had finalized an agreement to take over development of the compound.
PE: How can other companies benefit from taking promising research off the shelves of academia and bringing it into the clinic?
Henderson: Academia is chasing some of the greatest problems in disease research that biopharma companies simply don’t have the infrastructure or time to pursue. It’s astounding how much promising research is tucked away in institutions across the globe. As industry professionals, it’s up to us to collaboratively partner with these academics and provide insights into what we know best—drug development—to translate the findings into therapeutics for patients in need.
PE: You recently announced the acceptance of an NDA that treats an ultra-rare pediatric condition with a patient population of approximately 100-150. How is the experience of developing drugs for a small patient group different than for a large patient group?
Henderson: In a lot of ways, it’s the same. In terms of regulatory conversations and our NDA filing most recently, I can say for certain that the number of pages doesn’t decrease with the number of patients. But there is something truly special about working with such a small group of patients. There is the depth that you wouldn’t experience with bigger patient populations, as we get to know the patients, their families and experiences. As an industry, we always talk about focusing on patients, but working with such a small group allows us to truly live it.
When we launched this program, we didn’t expect it to have a huge market return. Some are perplexed by our decision, but at the end of the day, that’s not why we do what we do. We’re developing this drug because it’s what is right—the data shows promise, and patients’ lives depend on it.
This process has also shown us how to be nimble, creative, and do more with less. No matter the challenge, we always come back to our mission. What we’re doing here has never been done. Our work is also making history and setting the stage for others. If successful, we believe our treatment for MOCD Type A will be the smallest patient group to have a drug taken to the FDA just for them. We feel the outcome will be well worth conquering whatever roadblocks line the way.
PE: You’ve already accomplished so much and you’re only in your 30s. What do you think are the most pressing issues in rare disease drug development and what do you hope to achieve in the coming years?
Henderson: One of the most pressing issues is the lack of treatments available for patients with these chronic and, in many cases, life-threatening conditions. It’s especially frustrating when you realize how many of these diseases have clear genetic drivers that can directly inform targeted therapy development. As I mentioned before, these findings line the shelves of academia ready for biopharma to take them across the finish line. Patients’ lives depend on it.
Additionally, we’ve proven you don’t have to raise a $100 million Series A financing or hire hundreds of staff to successfully develop a drug. Your team should be tailored and focused on what matters, which is getting approved therapies to patients who need them. My hope for the remainder of my career is that we can show there is a more responsible, sustainable way to develop medicines for patients. I’d love if others replicated our model—we welcome competitors and believe there’s no shortage of work to be done.
My personal goal at BridgeBio is to contribute to 10 or more drug approvals, ensuring each of those approved medicines reaches all of the patients who need them. It’s why I do what I do.
Elaine Quilici is Pharm Exec’s Senior Editor. She can be reached at firstname.lastname@example.org.